Surface-Chemical Study on the Molecular mechanism of Amphiphilic Drug/Membrane Interaction

两亲性药物/膜相互作用分子机制的表面化学研究

基本信息

批准号：
05453059
负责人：
KANESHINA Shoji
金额：
$ 4.1万
依托单位：
The University of Tokushima
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05453059/
关键词：
Lipid bilayr Micelle Phase transition Pressure Local anesthetic Ion-selective electrode Mitochondria Vesicle

项目摘要

1) In order to elucidate the mechanism of pressure-anesthetic antagonism, we studied the effects of pressure and anesthetics on the phase-transition temperatures of dipalmitoyl-phosphatidylcholine (DPPC) bilayr membrane. Temperature of the pretransition, as well as the main transition, was elevated by pressure and depressed by anesthetics added. From the colligative thermodynamic framework, two kinds of differential partition coefficients were determined. The volume change due to the transfer of an anesthetic from the aqueous phase to the liquid crystal phase of DPPC membrane, which was evaluated from the pressure dependence of the partition coefficient for the liquid crystal phase, was 16-20 cm^3mol^<-1> according to the anesthetic.2) Interfacial adsorption of local anesthetics was studied by surface tension and density measurements. We suggested that the surface activity of local anesthetic is proportional to the facility of partitioning the anesthetic into membranes. The magnitude of surface activity (i.e.surface density) was in accord with the potency of the anesthetic action. The enthalpy change of phase transition from the coagel phase to the micellar solution for local anesthetics was determined directly from the DSC thermograms of anesthetic solutions. The molecular interaction of local anesthetics in membranes was studied thermodynamically.3) Binding of a local anesthetic dibucaine to dimyristoylphosphatidylcholine (DMPC) bilayr membranes was studied by means of an ion-selective electrode sensitive dibucaine cation. DMPC membranes undergo the thermotropic pretransition from the lamellar gel to the ripple gel phase in addition to the main transition from ripple get to the liquid crystal phase. Each of the three stanes exhibits a different receptivity to dibucaine partitioning.

1）为了阐明压力-麻醉拮抗机制，我们研究了压力和麻醉剂对二棕榈酰磷脂酰胆碱（DPPC）双层膜相变温度的影响。预转变以及主转变的温度因压力而升高，并因添加的麻醉剂而降低。从依数热力学框架出发，确定了两种微分分配系数。根据液晶相分配系数的压力依赖性来评估由于麻醉剂从水相转移到 DPPC 膜的液晶相而引起的体积变化为 16-20 cm^3mol^<- 1>根据麻醉剂。2)通过表面张力和密度测量来研究局部麻醉剂的界面吸附。我们认为，局部麻醉剂的表面活性与将麻醉剂分配到膜中的能力成正比。表面活性的大小（即表面密度）与麻醉作用的效力一致。局部麻醉剂从凝固凝胶相到胶束溶液的相变焓变直接由麻醉溶液的 DSC 热分析图确定。从热力学角度研究了局部麻醉剂在膜中的分子相互作用。3)通过离子选择电极敏感的丁布卡因阳离子研究了局部麻醉剂丁布卡因与二肉豆蔻酰磷脂酰胆碱(DMPC)双层膜的结合。除了从波纹相到液晶相的主要转变之外，DMPC 膜还经历从层状凝胶到波纹凝胶相的热致预转变。三种斯坦中的每一种都表现出对丁卡因分配的不同接受性。